New players in human BAT differentiation and activation: a human PSC-derived BAT approach combined with state of the art genome engineering and –omics based methodologies
|Title||New players in human BAT differentiation and activation: a human PSC-derived BAT approach combined with state of the art genome engineering and –omics based methodologies|
|Institution||Wellcome Trust - MRC Stem Cell Institute|
Associated cell lines
Here we propose a strategy to control body weight and prevent/reverse obesity based on targeting brown adipose tissue (BAT) to facilitate negative energy balance and prevent adaptive responses to dietary restriction. However, BAT in humans is limited and poorly characterised. Thus, we propose to use stem cells as a tool to gain unique insights into the biology of human brown adipocytes. The General Objective is to identify pathways and factors of potential therapeutic relevance that promote BAT development and/or activation/recruitment using a stem cell based BAT differentiation approach, and then to functionally validate the role of these factors in vitro by genome engineering human stem cell derived adipocytes and in vivo by transplanting these cells into mice. Specific Aims are: 1.To identify molecular mechanisms involved in human brown adipose tissue development and activation. 2. To investigate the molecular mechanisms involved in human white adipose tissue browning/brite cells recruitment 3. To identify new agents/compounds of therapeutic value, able to activate or recruit human brown adipose tissue/brite cells.